<i>HFE</i>Genotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

Acton, Ronald T.; Barton, James C.

doi:10.1089/109065701753617426

Cited by 8 publications

(3 citation statements)

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“…Thus, we observed a greater number of haplotypes which were significantly increased in frequency among the present Alabama hemochromatosis probands than have been reported in other hemochromatosis populations, including a cohort in Utah [16]. This could be attributed to a greater degree of genetic heterogeneity among whites in Alabama, consistent with previous reports of genetic characteristics of persons with hemochromatosis in this geographic area [23,45]. Alternatively, we had greater power to achieve statistical significance in the present analyses than did some other studies.…”

Section: Discussionsupporting

confidence: 90%

HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFEC282Y homozygosity in central Alabama

Barton

Acton

2002

BMC Med Genet

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Section: Discussionsupporting

confidence: 90%

HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFEC282Y homozygosity in central Alabama

Barton

Acton

2002

BMC Med Genet

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“…Diagnosis and treatment of H/IO before initial screening could partly explain these observations. Many common medical conditions such as liver disorders or diabetes also cause elevated TS or SF [30,31,33,[35][36][37][38][39][40][41][42][43][44][45][46][47] which can lead to misdiagnosis of H/IO [30,45,48]. The HEIRS Study initial screening form did not permit reporting of factors needed to assess iron nutrition and balance, including diet, iron intake, reproductive and menstrual history, anemia, receipt of erythrocyte transfusion, therapeutic phlebotomy, liver or bone marrow biopsy, blood donation, or illness associated with blood loss [22].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of participants with self‐reported hemochromatosis or iron overload at HEIRS study initial screening

et al. 2007

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There are few descriptions of young adults with self-reported hemochromatosis or iron overload (H/IO). We analyzed initial screening data in 7,343 HEmochromatosis and IRon Overload Screening (HEIRS) Study participants ages 25-29 years, including race/ethnicity and health information; transferrin saturation (TS) and ferritin (SF) measurements; and HFE C282Y and H63D genotypes. We used denaturing high-pressure liquid chromatography and sequencing to detect mutations in HJV, TFR2, HAMP, SLC40A1, and FTL. Fifty-one participants reported previous H/IO; 23 (45%) reported medical conditions associated with H/IO. Prevalences of reports of arthritis, diabetes, liver disease or liver cancer, heart failure, fertility problems or impotence, and blood relatives with H/IO were significantly greater in participants with previous H/IO reports than in those without. Only 7.8% of the 51 participants with previous H/IO reports had elevated TS; 13.7% had elevated SF. Only one participant had C282Y homozygosity. Three participants aged 25-29 years were heterozygous for potentially deleterious mutations in HFE2, TFR2, and HAMP promoter, respectively. Prevalences of selfreported conditions, screening iron phenotypes, and C282Y homozygosity were similar in 1,165 participants aged 30 years or greater who reported previous H/IO. We conclude that persons who report previous H/IO diagnoses in screening programs are unlikely to have H/IO phenotypes or genotypes. Previous H/IO reports in some participants could be explained by treatment that induced iron depletion before initial screening, misdiagnosis, or participant misunderstanding of their physician or the initial screening questionnaire. Am. J. Hematol. 83:126-132, 2008. V

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“…This is true for the interpretation of HFE genotype results and for offering guidance about the significance of the results for first‐degree relatives. Previously reported experience with integrating clinical indications for HFE testing with genotype results has revealed the high utility of HFE test results for patients in whom testing is clinically justifiable 13 . As a prelude to integrating prior‐risk data obtained from clinical details into HFE genotype reports, we retrospectively audited the clinical rationale for a consecutive series of samples forwarded for testing to our pathology service.…”

Section: Discussionmentioning

confidence: 99%

Directions for clinical practice improvement in HFE gene mutation testing

Gillett

Mamotte

Ravine

et al. 2007

Medical Journal of Australia

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Researchnumber of inherited and acquired disorders may result in iron overload; hereditary haemochromatosis (HH) is the most frequent in populations of northern European descent. HH was previously regarded as a distinct clinical entity with a single genetic aetiology. The discovery of HH-causative mutations in the HFE gene 1 revealed that both these assumptions were wrong.HH is usually associated with homozygosity for the C282Y mutation in the HFE gene. 2 However, one in eight healthy Australians are heterozygous carriers of C282Y 3 and one in four are carriers of an H63D mutation, 4 which must be considered when interpreting HFE genotype results in patients with iron overload. Although homozygosity for the C282Y mutation was thought to predispose people to severe organ damage from excessive iron accumulation, a number of studies have shown that only in a minority of cases do people develop severe clinical disease or organ damage. 3,[5][6][7][8][9] From a clinical perspective, it is now evident that HFE mutations are not responsible for all cases of HH; other genes contributing to iron homeostasis have been identified, 2 although homozygosity for C282Y predominates among Australian HH patients, most of whom have western European ancestry. 10 Biochemical testing for iron overload and genetic testing for HFE status are handled differently. The former will confirm or rule out current iron overload, while HFE testing, depending on the prior risk, will give a post-test probability of the patient developing iron overload. Clinical interpretation of HFE genotypes found in patients being investigated for iron overload and interpretation of HFE results in healthy first-degree relatives of a newly diagnosed patient can therefore vary substantially.In our laboratory, we seek to offer appropriate guidance by including interpretive comments with our HFE genotype test results. However, in the absence of clinical details on the request form (a not uncommon occurrence) and relevant biochemical details, this is not always possible. With the objective of improving the quality of our HFE genotype reports, we retrospectively audited the clinical indications for a consecutive series of requests. METHODSWe reviewed all requests for HFE genotyping received by the Biochemical Genetics Laboratory at Royal Perth Hospital (RPH) over a 25-month period (June 2003 -June 2005. The audit was registered with the Quality Unit in the RPH Division of Laboratory Medicine. Samples were forwarded either by doctors within RPH or from doctors (predominantly general practitioners) external to the hospital. When the clinical reason for the test had not been provided, the notes of hospital cases were reviewed, and external referring doctors were contacted directly.Reasons prompting the requests for HFE genotyping were then audited for compliance with the indications specified in the Australian Medicare Benefits Schedule (MBS), 11 which are: • elevated transferrin saturation or serum ferritin level on testing of repeated specimens; • a first-degree relativ...

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HFEGenotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

Cited by 8 publications

References 51 publications

HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFEC282Y homozygosity in central Alabama

HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFEC282Y homozygosity in central Alabama

Characteristics of participants with self‐reported hemochromatosis or iron overload at HEIRS study initial screening

Directions for clinical practice improvement in HFE gene mutation testing

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